Open AccesscAMP response element‐binding protein and Yes‐associated protein form a feedback loop that promotes neurite outgrowth
Author(s) -
Chen Lei,
Feng Peimin,
Peng Anjiao,
Qiu Xiangmiao,
Zhu Xi,
He Shixu,
Zhou Dong
Publication year - 2018
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.13324
Subject(s) - creb , neurite , cyclic amp response element binding protein , microbiology and biotechnology , retinoic acid , transcription factor , biology , cell culture , in vitro , genetics , gene
The cAMP response element‐binding (CREB) protein is a member of the CREB/activating transcription factor family that is activated by various extracellular stimuli. It has been shown that CREB‐dependent transcription stimulation plays a key role in neuronal differentiation and plasticity, but the underlying mechanisms remain largely elusive. Here, we show that Yes‐associated protein (YAP) is a direct target induced by CREB upon retinoic acid (RA)‐induced neurite outgrowth stimuli in N2a cells. Interestingly, YAP knockout using the CRISPR/Cas9 system inhibits neuronal differentiation and reduced neurite length. We further show that YAP could directly bind to CREB via its N‐terminal region, and loss of YAP results in instability of phosphorylated CREB upon neurite outgrowth stimuli. Transient expression of YAP could largely restore CREB expression and neurite outgrowth in YAP knockout cells. Together, our results suggest that CREB and YAP form a positive feedback loop that is critical to maintain the stability of phosphorylated CREB and promote neurite outgrowth.